title: An important role for the retinoblastoma protein in staurosporine-induced G1 arrest in murine embryonic fibroblasts.
abstract: In this study, we investigated the molecular basis of the ability of staurosporine to induce G1 arrest in murine embryonic fibroblasts (MEFs). We used MEFs from transgenic mice lacking several negative regulators of the G1/S phase transition including cells from mice lacking p53, p21, retinoblastoma (Rb), or p16 genes. We found that p53 function was not essential for staurosporine-induced G1 arrest. In contrast, MEFs from mice lacking Rb genes showed approximately a 70% reduced capacity to arrest in the G1 phase following staurosporine treatment. In support of a role for Rb in staurosporine-induced G1 arrest, rat embryonic fibroblasts stably overexpressing cyclin D1/Cdk4(R24C) exhibited approximately a 50% reduced G1 arrest response to staurosporine. The role of Rb in determining the degree of staurosporine-induced G1 arrest did not depend on the function of the cyclin-dependent kinase inhibitors p16 or p21 because MEFs lacking either of these genes were still capable of undergoing G1 arrest following staurosporine exposure. Our studies provide evidence of an important role for the Rb protein in determining the degree of staurosporine-induced G1 arrest in the first cell cycle.
authors.affiliation: Laboratory of Molecular Pharmacology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Orr
authors.forename: W
authors.initials: W
authors.lastname: Reinhold
authors.forename: L
authors.initials: L
authors.lastname: Yu
authors.forename: N
authors.initials: N
authors.lastname: Schreiber-Agus
authors.forename: P M
authors.initials: PM
authors.lastname: O'Connor
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D005347:Fibroblasts; D005434:Flow Cytometry; D016193:G1 Phase / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D016160:Retinoblastoma Protein / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology*; D013489:Suppression, Genetic / Q000235:genetics
chemical_list: D016160:Retinoblastoma Protein; D019938:Cyclin D1; D019311:Staurosporine